Hepatitis C viral infection in drug users

Authors


  • Potential conflict of interest: Diana L. Sylvestre is on the Speaker Bureau for Merck.

Abstract

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Abbreviations

HCV, hepatitis C virus; IDU, injection drug user; SVR, sustained virological response.

Although the majority of new hepatitis C virus (HCV) infections in the United States and globally are related to injection drug use, access to care and treatment remains disproportionately limited, and treatment efficacy data are still scanty. Many small studies, which usually have been performed in settings with expertise in the treatment of addiction, have reported that treatment outcomes for drug users are comparable to outcomes for non-drug users in registration trials, but concerns about adherence, comorbid mental illness, and reinfection remain barriers to intervention. However, with new treatment regimens holding promise for improved outcomes and reduced side effects in the future (when interferon might be avoided), a more careful consideration of treatment eligibility is becoming increasingly warranted.

Epidemiology

International estimates of the incidence of HCV in injection drug users (IDUs) range from 11 to 42 per 100 person-years, and the prevalence is as high as 93%1-3 (Fig. 1). Non-IDUs are also at increased risk, although the evidence remains controversial; studies have suggested a variety of reasons for the increased risk, including unreported injecting behaviors, unsafe tattoos, risky sexual behaviors, and the sharing of non-injecting equipment (e.g., straws and crack pipes). There is substantial variation in reported prevalence rates in non-injectors (2.3%-35.3%).4

Figure 1.

Estimated prevalence of HCV in various drug-using populations.

Natural History

Assessing the risk of progression to cirrhosis is the fundamental criterion for determining the need for HCV antiviral therapy. The natural history of HCV in drug users may be accelerated by higher rates of human immunodeficiency virus and hepatitis B virus coinfections as well as concurrent alcohol abuse. A recent meta-analysis of 47 studies indicated that the rate of progression to cirrhosis for patients with HCV acquired through injection drug use was 8.1 per 1000 person-years, which corresponded to a 20-year prevalence of cirrhosis of 14.8%.2 In this analysis, progression was associated with male sex and excessive alcohol use (but not human immunodeficiency virus). This is well within the range of general 20-year cirrhosis prevalence estimates for HCV patients (7%-18%)5 and supports the idea that abused drugs other than alcohol do not meaningfully affect the natural history of HCV infection.

Treatment

Decisions about treating drug users for HCV are difficult because of the many potential barriers that are either unique to these persons or more prevalent in this population. These include high rates of mental health issues, concerns about relapse to or concurrent drug or alcohol use, and psychosocial instability; each of these has the potential to affect adherence and treatment completion rates. In addition, high rates of reinfection in those who continue to practice unsafe injecting may make treatment futile. However, existing clinical data indicate that when drug users are treated within a setting that can address their needs, these concerns may be appropriately addressed, and the treatment outcomes are similar to those of non-drug users.

Adherence

In the era of direct-acting antiviral agents, careful adherence to the medication regimen is needed to reduce the potential for the development of viral resistance. Although data are limited, studies indicate that the compliance rates of drug users are similar to those of non-drug users. In a recent review, the rate of noncompliance was 6.8% overall for IDUs and 4.9% for non-drug users,6 and only one study to date has shown a statistically significant difference between the two groups.7 Similarly, treatment completion rates also appear to be similar in IDUs and non-IDUs. In studies that allowed a comparison of the two groups, 79.4% of non-IDUs and 70.9% of IDUs completed treatment.6

A related adherence measure is the treatment completion rate; again, the rates of treatment completion appear to be similar in IDUs and non-drug users. A review of studies that compared the two groups showed that 70.9% of IDUs and 79.9% of non-IDUs completed treatment. Among the five studies that directly compared these completion rates, only one study with 81 patients found that there was a statistically significant difference.6

Outcomes

As shown in Table 1, the rates of sustained virological response (SVR) for IDUs in studies using pegylated interferon and ribavirin have varied widely and have ranged from a low of 18.1% in a prospective US study that enrolled 447 IDUs at Veterans Administration centers9 to a high of 94.1% in a study that enrolled 17 IDUs on methadone treatment in Norway.11 Studies including non-IDU comparator arms have shown that treatment outcomes are statistically similar for the two cohorts, with the SVR rates for IDUs being similar to and sometimes higher than the rates for non-IDUs.6

Table 1. IDU Treatment Outcomes With Pegylated Interferon and Ribavirin
StudyCohortPatients (n)SVR (%)Significance
Mauss et al.7 (2004)IDUs5042No
Non-IDUs5056
Neri et al.17 (2007)IDUs10762.6Not tested
Non-IDUs5276.9
Schaefer et al.18 (2007)IDUs1872.2No
Former IDUs1353.8
Non-IDUs3953.8
Seal et al.9 (2007)IDUs44718.1No
Non-IDUs34818
Thomson et al.10 (2008)IDUs20558.5No
Non-IDUs14260.6

Acute HCV

Although most cases of acute HCV today occur in IDUs, they are grossly underrepresented in acute HCV treatment studies because of challenges related to identifying and engaging active drug users at the time of viral acquisition and because of misperceptions about treatment candidacy. In the three published studies that specified the total number of acute HCV cases and did not exclude current IDUs from treatment initiation,12–14 20 of 50 IDUs (40%) and 11 of 14 non-IDUs (79%) initiated treatment. In six published studies of the treatment of acute HCV with various interferon-based regimens that did not exclude active injectors, 54 of 82 IDUs (66%) and 39 of 46 non-injectors (85%) attained SVR.6

Reinfection

There are limited data on rates of reinfection after successful HCV treatment, but these numbers appear to be low. The reasons for this remain unclear but are possibly related to enhanced immunity or safer drug use practices. In one study that followed 27 IDUs for 13 to 82 months (median = 65 months) after treatment completion, 9 relapsed to injection drug use. Their rate of reinfection was 2.5 cases per 100 person-years.15 Another study that followed 18 former IDUs for 58 person-years after treatment showed a reinfection rate of 0 to 2 cases per 100 person-years.16

Summary

Although drug users represent the majority of new and existing cases of HCV, there are relatively limited data on adherence, treatment candidacy and uptake, and outcomes. However, existing data support the contention that these rates are similar and that drug users should be offered treatment according to standard natural history considerations and should not be excluded from treatment because of unfounded concerns about reduced adherence and reinfection. Clearly, treatment outcomes can be optimized by careful attention to psychosocial factors that have the potential to influence access to care and compliance with therapy.

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